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Completed

NCT Number: NCT02230800

PPALM-Palm Oil and Pentoxifylline Against Late Morbidity

Side effects are common after treatment with radiotherapy for tumours in the pelvis and can affect the way the bowel and urinary system work as well as causing sexual difficulties, skin damage and bone problems. Problems in the bowel, bladder, sexual organs and skin mostly result from thickening of the tissues in response to radiotherapy, a process called "fibrosis". Fibrosis often worsens over time.

There has been progress in treating bowel symptoms which usually are the worst problem after radiotherapy. However, even after receiving the best possible treatments, while many patients are better, they are often not cured of all their difficult problems.

For some years, it has been hypothesised that if fibrosis could be treated then symptoms would improve. Recent research in laboratory animals has suggested that an effective treatment for radiation-induced fibrosis is combination therapy with a drug called Pentoxifylline together with a nutritional supplement containing gamma-tocotrienol (Tocovid SupraBio), a substance derived from palm oil. Both of these agents are simple to take and side effects are rare.

This study will recruit volunteers who continue to have difficult side effects after previous radiotherapy to the pelvis despite receiving the best treatments available from a unique clinic at The Royal Marsden which has pioneered treatment for bowel problems after radiotherapy. Two out of every three volunteers who take part, will be randomly assigned to treatment with Pentoxifylline and Tocovid SupraBio, while one out of three will receive dummy pills. Neither the patients nor the staff assessing them will know which treatment they have been given. Volunteers take the active treatments or dummy tablets for a year and will be assessed regularly while on treatment and for a year afterwards. This study will show whether active treatment is more effective than dummy pills in improving the symptoms caused by radiation-induced fibrosis.

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Key information

Conditions

Long-term Adverse Effects of Radiotherapy for Pelvic Cancer

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

-

  • Age over 18 years.
  • Past history of a malignant pelvic neoplasm (T1-4 N0-2 M0) of the rectum, prostate, testis, bladder, uterine cervix, uterus, vagina, vulva, anal canal or ovary.
  • A minimum 12 months follow-up post-radiotherapy (24 months for patients with past history of stage T4 and/or N2 disease).
  • A maximum 7 years post-radiotherapy
  • No evidence of cancer recurrence.
  • Gastrointestinal symptoms attributable to prior radiotherapy: grade 2 or higher in any CTCAE Version 4 category, or grade 1 with difficult intermittent symptoms.
  • Symptoms are not relieved by appropriate life-style advice and medication over a 3-month period.
  • Physical and psychological fitness for Tocovid SupraBio+PTX therapy.
  • Written informed consent and availability for follow up.
  • Willingness to keep to a specified level of dietary fat intake during the study.

Exclusion criteria

-

  • Surgery for rectal cancer.
  • Contra-indication or other inability to undergo magnetic resonance imaging, if required to rule out malignancy.
  • Dietary supplementation containing alpha-tocopherol above a daily dose of 30mg at any time during the last three months.
  • Medication with pentoxifylline at any time since radiotherapy.
  • Pregnancy or breast feeding.
  • Ischaemic heart disease, uncontrolled hypertension, hypotension, acute myocardial infarction, cerebral haemorrhage, retinal haemorrhage, renal failure, liver failure and medication with insulin, ketorolac or vitamin K.
  • Allergy to soya.
  • Known hypersensitivity to the active constituent, pentoxifylline other methyl xanthines or any of the excipients', as per SmPC for pentoxifylline.

Treatment and study plan

Tocovid SupraBio plus pentoxifylline

Drug

Matching placebos

Drug

Primary outcomes

  1. Change at 12 months in the bowel disease subset of the Modified IBDQ Quality of Life questionnaire.

    Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.

Secondary outcomes

  1. Change at 12 months in rectal IBDQ bleeding score between the two groups in those patients presenting with grade 2, 3 or 4 bleeding.

    Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.

  2. Change at 12 months in IBDQ faecal incontinence score between the two groups in those patients presenting with grade 1 or greater incontinence.

    Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.

  3. Proportion of items graded as marked or severe (grade 3 or 4).

    Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.

  4. Physician assessment of rectal dysfunction based on the modified CTCAE Version 4 grading.

    Time frame: Endpoint will be assessed pre-treatment and 6, 12 & 24 months post-treatment.

  5. Patient self-assessments: QLQ-C30 and CR29 and the Gastrointestinal Symptom Rating Scale.

    Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.

  6. Photographic assessment of rectal mucosa.

    Time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment

  7. Serum fibrosis marker levels.

    Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.

Other outcomes

  1. Translational endpoint: Rectal biopsies (optional)

    Time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment.

    Tissue samples will be banked until after the final analysis of the trial, when funding will be sought to identify molecular and cellular correlates of therapeutic response in the event of a statistically significant benefit for Tocovid SupraBio/ PTX combination.

  2. Translational endpoint: Blood samples

    Time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment.

    Development of novel markers of fibrosis.

Sponsors and collaborators

Lead sponsor

Royal Marsden NHS Foundation Trust

Other

Collaborators

  • Malaysia Palm Oil Board

Registry information

Official study title

Randomised Double-blind Placebo Controlled Phase II Trial of Tocovid SupraBio in Combination With Pentoxifylline (PTX) in Patients Suffering Long-term Adverse Effects of Radiotherapy for Pelvic Cancer

Acronym: PPALM

Important dates

Study start
2014
Primary completion
2019
Study completion
2019
First posted
Sep 3, 2014
Registry last updated
Dec 23, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.